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ProteinuriaProteinuria The primary care approach Presented by feras ghosheh feras ghosheh 6 th Y medical student AL-QUDS UNIVERSITY 4MedStudents.com.

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Presentation on theme: "ProteinuriaProteinuria The primary care approach Presented by feras ghosheh feras ghosheh 6 th Y medical student AL-QUDS UNIVERSITY 4MedStudents.com."— Presentation transcript:

1 ProteinuriaProteinuria The primary care approach Presented by feras ghosheh feras ghosheh 6 th Y medical student AL-QUDS UNIVERSITY 4MedStudents.com

2 Proteinuria INTRODUCTION DEFINITION EPIDEMIOLOGY PATHOGENESIS DIFFERENTIAL DIAGNOSIS CLINICAL FEATURES Specific Entities INVESTIGATIONS MANAGEMENT 4MedStudents.com

3 INTRODUCTION The protein is found in normal urine, and its divided into: 1-60% plasma proteins: albumin (major) IgG, IgA,light chains,heavy chains, transferrin,haptoglobin,lysozyme,amylaze,kallikrein % originating from the secretions of the urinary tract including: tamm-horstall,urokinase and secertory IgA. The reasonable upper limit of normal protien excretion in healthy children = 150 mg/24 hrs.

4 DEFINITION The excretion of an excessive amount of protein (>150mg/day) in the urine as defined by qualitative, semi-quantitative, and quantitative methods. The excretion of an excessive amount of protein (>150mg/day) in the urine as defined by qualitative, semi-quantitative, and quantitative methods.

5 EPIDEMIOLOGY incidence: 1 - 5% (depend upon age and number of samples) prevalence: % (1+ proteinuria) only 10% of kids with proteinuria will have abnormalities after 6-10 month of follow-up of those children with isolated proteinuria, <2% will have significant underlying renal disease the incidence of proteinuria in patients with underlying renal disease is remarkably high

6 PATHOGENESIS There are three basic types of proteinuria : 1-glomerular 2-tubular 3- overflow

7 1. Glomerular mechanisms: mechanisms:. increased GFR. increased GFR. increased glomerular permeability. increased glomerular permeability basement membrane basement membrane endothelial, epithelial cell injury endothelial, epithelial cell injury electrostatic charge barrier electrostatic charge barrier proteins: larger macromolecules, albumin proteins: larger macromolecules, albumin

8 2. Tubulointerstitial impaired tubular reabsorption of filtered proteins impaired tubular reabsorption of filtered proteins proteins: low MW proteins, lysozyme, B2-microglobulin proteins: low MW proteins, lysozyme, B2-microglobulin Tamm-Horstall protein Tamm-Horstall protein

9 3. Overload Proteinuria increased load overloads tubular reabsorptive capacity increased load overloads tubular reabsorptive capacity proteins: low MW plasma proteins, Ig light chains, myoglobulin, lysozyme, albumin proteins: low MW plasma proteins, Ig light chains, myoglobulin, lysozyme, albumin

10 1. Benign Proteinuria a. Benign Transient Proteinuria b. Orthostatic Proteinuria c. Persistent Asymptomatic Proteinuria

11 2. Pathologic Proteinuria A- Glomerular 1. Hereditary 1. Hereditary 2. Non-Hereditary 2. Non-HereditaryB-Tubulointerstitial 1. Hereditary 1. Hereditary 2. Non-Hereditary 2. Non-Hereditary

12 A- Glomerular 1. Hereditary Congenital Nephrotic Syndrome Alport Syndrome 2. Non-hereditary 1. Acute (GN ) -Poststrep GN -H.U.Syndrome -H.S. Purpura 2. Chronic 1. Primary Minimal Change Disease* FSGN Mesangioproliferative GN Membranous GN Membranoproliferative GN 2. Secondary Berger (IgA) Nephropathy Goodpastures Nephropathy SLE Nephropathy Wegeners Nephropathy Diabetic Nephropathy Renal Vein Thrombosis Sickle Cell Disease

13 B-Tubulointerstitial 1.Hereditary Cystinosis Galactosemia Lowe Syndrome Medullary Cystic Kidney Proximal RTA Wilson Disease 2. Non-Hereditary Acute Tubular Necrosis analgesic abuse antibiotics cystic diseases heavy metal poisoning homograft rejection hypokalemia interstitial nephritis penicillamine reflux

14 3. Overload Proteinuria 1. Neoplastic Amyloidosis Leukemia (monocytic, monomyelocytic) - lysozymuria Multiple Myeloma Waldenstrom's Macroglobinemia 2. Others IDDM (microalbuminuria) repeated albumin or blood transfusions Rhabdomyolysis most common causes of proteinuria in childhood

15 CLINICAL FEATURES: 1. History of Presenting Illness at the end of the history, one should be able to discern: 1. benign vs pathologic proteinuria (if pathologic then) 2. glomerular vs tubulointerstitial proteinuria (if glomerular then) 3. hereditary vs non-hereditary (if non-hereditary then) 4. acute GN vs chronic GN (if chronic then) 5. primary GN vs secondary GN 6. nephrotic vs non-nephrotic proteinuria 7. proteinuria with or without hematuriauria onset when began with conditions identified around the initial presentation, i.e., drug ingestion record of previous urinalyses precipitation/palliation identification of triggering agents infectious, drugs, foods, chemicals, vaccinations helps to identify acquired forms of tubulointerstitial proteinuria

16 quality quality associated with hematuria severity severity more likely to be pathologic proteinuria if associated with hematuria or Nephrotic Syndrome (edema, hypoalbuminemia, hypercholesterolemia) if Nephrotic Syndrome present: likely to be a primary GN unlikely to be benign etiology or secondary GN timing timing acute vs acute-on-chronic intermittent vs persistent duration of proteinuria associated symptoms associated symptoms past medical history functional inquiry helps to differentiate acute GN from chronic GN helps to identify overload proteinuria causes

17 Family History helps to differentiate hereditary from non-hereditary forms of both glomerular and tubulointerstitial forms of proteinuria: 1. Proteinuria family members must have had previous urinalysis to ascertain this 2. Renal Disease Polycystic Kidney Disease Nephrotic Syndrome, Fanconi Disease renal dialysis kidney transplantation 3. Others hearing/ocular impairment (Alport Syndrome)

18 Specific Entities 1. Benign Transient Proteinuria benign proteinuria associated with precipitating factors - fever, exercise, stress, cold weather, dehydration, high blood pressure, seizures, etc Orthostatic Proteinuria2. diagnosis based upon the Postural Test has a benign clinical course

19 3. Persistent Asymptomatic Proteinuria proteinuria that persists for 3-6 months proteinuria that persists for 3-6 months renal biopsy after 6 months of persistent proteinuria and if FSGS then at risk for chronic renal failure renal biopsy after 6 months of persistent proteinuria and if FSGS then at risk for chronic renal failure 4. Congenital Nephrotic Syndrome onset at birth with Nephrotic Syndrome (massive proteinuria, hypoalbuminemia, edema, and hyperlipidemia) onset at birth with Nephrotic Syndrome (massive proteinuria, hypoalbuminemia, edema, and hyperlipidemia) very difficult to treat with poor prognosis very difficult to treat with poor prognosis 5. Poststreptococcal GN proteinuria + hematuria proteinuria + hematuria associated symptoms prodrome of pharyngitis, URTI, impetigo prodrome of pharyngitis, URTI, impetigo Nephrotic and/or Nephritic Syndrome

20 6. Hemolytic Uremic Syndrome 6. Hemolytic Uremic Syndrome proteinuria + hematuria proteinuria + hematuria associated symptoms associated symptoms prodrome of bloody diarrhea prodrome of bloody diarrhea anemia and thrombocytopenia (petechiae) anemia and thrombocytopenia (petechiae) Nephrotic and/or Nephritic Syndrome Nephrotic and/or Nephritic Syndrome 7. Henoch-Schoenlein Purpura 7. Henoch-Schoenlein Purpura proteinuria + hematuria proteinuria + hematuria associated symptoms associated symptoms purpuric rash, arthritis, abdominal pain purpuric rash, arthritis, abdominal pain Nephrotic and/or Nephritic Syndrome Nephrotic and/or Nephritic Syndrome 8. Primary Glomerulonephritis 8. Primary Glomerulonephritis isolated proteinuria +/- Nephrotic Syndrome isolated proteinuria +/- Nephrotic Syndrome associated symptoms associated symptoms edema, hypoalbuminemia, hyperlipidemia edema, hypoalbuminemia, hyperlipidemia

21 9. Secondary Glomerulonephritis proteinuria +/- hematuria associated with a disease entity, i.e., SLE, Goodpastures Disease, Wegeners Disease, Diabetes Mellitus proteinuria +/- hematuria associated with a disease entity, i.e., SLE, Goodpastures Disease, Wegeners Disease, Diabetes Mellitus 10. Hereditary Tubulointerstitial Proteinurias tubular proteinuria tubular proteinuria associated symptoms associated symptoms episodes of vomiting, dehydration, weakness, fever, anorexia, constipation, failure to thrive, polydipsia, polyuria

22 INVESTIGATIONS 1. Proteinuria (Diagnosis) 1. Qualitative - Dipstick measures a range of protein concentrations depth of colour increases in a semiquantitative manner with increasing urinary protein concentration to rule out false positives must have: 3 samples with proteinuria first voided early morning samples pH < 6.0 with known specific gravity 1+ ( mg/24 hrs) or greater is considered abnormal dependent on specific gravity of urine sample FP: gross hematuria, highly alkaline urine, UTI

23 2. Semi-quantitative - Protein/Creatinine Ratio in Urine random early morning single voided specimen children < 2 years : < 0.5 children > 2 years : < 0.2 nephrotic : > 3.5 correlates with the 24 hour protein excretion data

24 3. Quantitative - 24 hr. urine collection gold standard gold standard if dipstick is 1+ or more than obliged to do a 24 hour urine collection if dipstick is 1+ or more than obliged to do a 24 hour urine collection 24 hr. urine collection 24 hr. urine collection Protein (mg)/m2/hr Protein (mg)/m2/hr < 4 mg/m2/hourr (normal) < 4 mg/m2/hourr (normal) 4-40mg/m2/hour (proteinuria) 4-40mg/m2/hour (proteinuria) 40 mg/m2/hour (nephrotic) 40 mg/m2/hour (nephrotic) Protein (mg)/24 hr Protein (mg)/24 hr 2 to 12 months : > 155 mg/24 hr 2 to 12 months : > 155 mg/24 hr 3 to 4 years : > 140 mg/24 hr 3 to 4 years : > 140 mg/24 hr 4 to 10 years : > 190 mg/24 hr 4 to 10 years : > 190 mg/24 hr 10 to 16 years : > 250 mg/24 hr 10 to 16 years : > 250 mg/24 hr FP: radiographic contrast media, cephalosporins, pencillin analogues, sulfonamide metabolites FP: radiographic contrast media, cephalosporins, pencillin analogues, sulfonamide metabolites

25 2. Indications for Further Investigation Non-orthostatic Proteinuria Persistent Proteinuria Symptomatic (edema, elevated BP, abdominal pain, hematuria)

26 3. First Line Investigations 1. Urinalysis R&M, C&S, microscopy orthostatic test 24 hour collection total protein creatinine clearance 2. Serum electrolytes, BUN, creatinine, albumin, cholesterol, triglyceride, calcium, protein, CBC orthostatic test 4. Second Line Investigations 1. Urine protein electrophoresis can be used to differentiate glomerular (albumin) from tubular (Tamm- Horstall) proteinuria 2. Serum IgA, PTH, ANA, protein electrophoresis, ASOT, anti-GBM antibodies, uric acid, C3, C4 3. Imaging Studies renal ultrasound to rule out renal vein thrombosis 4. Renal Biopsy indicated for: progressive proteinuria with hematuria all forms of Nephrotic Syndrome except that caused by steroid- responsive Minimal Change Disease

27 MANAGEMENT treat underlying disorder treat complications

28 Thank you 4MedStudents.com


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